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Updated: May 17, 2026
In Vitro Differentiation of Human Mesenchymal Stem Cells into Functional Cardiomyocyte-like Cells
Published on: August 9, 2017
Genetically Engineered Mesenchymal Stem Cells Influence Gene Expression in Donor Cardiomyocytes and the Recipient
Mary Kearns-Jonker1, Wangde Dai, Mirja Gunthart
1Dept of Cardiothoracic Surgery, Childrens Hospital Los Angeles, Los Angeles, CA, USA ; Dept of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, CA, USA.
Combination therapy with human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and mesenchymal stem cells (MSCs) overexpressing heme oxygenase-1 (HO-1) promotes cardiac repair. This approach enhances pro-survival and angiogenesis genes in transplanted cells and host cardiac markers.
Area of Science:
- Regenerative Medicine
- Cardiovascular Biology
- Stem Cell Therapy
Background:
- Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and mesenchymal stem cells (MSCs) show potential for post-myocardial infarction recovery.
- The synergistic effects of co-transplanting hESC-CMs with MSCs, particularly those engineered for enhanced survival, remain largely unexplored.
Purpose of the Study:
- To investigate gene expression changes in donor and host cells following co-transplantation of hESC-CMs with and without MSCs engineered to overexpress heme oxygenase-1 (HO-1).
- To assess the impact of this combination therapy on cardiac function and tissue repair mechanisms.
Main Methods:
- Human MSCs were genetically modified to overexpress HO-1 using lentiviral vectors.
- Athymic nude rats underwent myocardial infarction and received treatments: hESC-CMs alone, hESC-CMs + unmodified MSCs, hESC-CMs + HO-1 overexpressing MSCs, or saline.
- Gene expression was analyzed using real-time PCR; cardiac function was evaluated by angiography.
Main Results:
- Co-transplantation with MSCs (unmodified or HO-1 overexpressing) alongside hESC-CMs significantly increased expression of pro-survival and pro-angiogenic genes (CXCR4, HGF, IGF, VEGF, TGF-β, CCL2, SMAD7, STAT3) compared to hESC-CMs alone.
- The HO-1 MSCs group showed the highest levels of these genes and cardiomyocyte transcription factors at 30 days post-transplantation.
- Elevated expression of cardiac (NKX2.5, troponin T), endothelial (CD31), and stem cell markers (CD34, isl-1, c-kit) was observed in both human and rodent cells, alongside induced cell cycle genes. Ejection fraction improved by 6-7%.
Conclusions:
- Co-administration of HO-1 overexpressing MSCs with hESC-CMs enhances pro-survival and angiogenesis-promoting gene expression in transplanted cells.
- This combination therapy also upregulates cardiac and endothelial cell markers in the host heart, indicating activated tissue repair.
- The findings suggest a potent therapeutic strategy for myocardial infarction by combining stem cell types with enhanced survival properties.
